Serum total cortisol and free cortisol index give different information regarding the hypothalamus–pituitary–adrenal axis reserve in patients with liver impairment

This version was published on 1 November 2009

Ann Clin Biochem 2009;46:505-507
© 2009 Association for Clinical Biochemistry


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Short Reports

Royce P Vincent1,
Frédérique E Etogo-Asse2,
Tracy Dew1,
William Bernal2,
Jamshid Alaghband-Zadeh1 and
Carel W le Roux1

1 Department of Chemical Pathology;
2 Institue of Liver Studies, King’s College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK

Corresponding author: Dr Carel W le Roux. Email: c.leroux{at}

Background: The short synacthen test (SST) is used to investigate patientswith suspected hypothalamus–pituitary–adrenal (HPA)axis pathology. A rise of serum total cortisol (total cortisol)above 550 nmol/L is accepted as sufficient adrenal reserve.In total, 80% of cortisol is bound to cortisol-binding globulin(CBG) and 10% to albumin. In the acute phase responses CBG concentrationsdecrease and can influence the interpretation of SST. The freecortisol index (FCI) is a surrogate marker for free cortisoland is defined as total cortisol (nmol/L)/CBG (mg/L) with anFCI > 12 representing sufficient adrenal reserve. The aimof this study was to compare total cortisol and FCI in the interpretationof SST in patients with liver impairment.

Method: SST was done on 26 patients with liver impairment. Total cortisolwas measured on Advia Centaur; serum CBG by radioimmunoassayand FCI calculated.

Results: Eleven (42%) patients had a total cortisol >550 nmol/L (range555–2070) and FCI > 12 (12.0–68.9) suggestingsufficient cortisol reserve. Three patients (13%) had totalcortisol <550 nmol/L (268–413) and FCI < 12 (3.5–11.6)consistent with cortisol deficiency. Twelve patients (46%) hada total cortisol <550 nmol/L (144–529), but an FCI> 12 (12.0–52.9). None of the patients had a totalcortisol >550 nmol/L and FCI < 12.

Conclusion: When total cortisol alone is used to interpret SST in patientswith liver impairment, 46% may have been classified as havingadrenal insufficiency because of low CBG. FCI may be betterfor the evaluation of HPA axis insufficiency in patients withliver impairment.

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